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Research in the Thorn-Seshold Group

We use chemical biology to develop stimulus-responsive reagents for both research and therapeutic applications. This fascinating and challenging goal brings together organic synthesis, biochemistry, cell biology, and in vivo biology.

Light, chemistry, biology: Photoresponsive drugs for controlling biology
The precision and power of optical imaging have been massive drivers of modern biology; so too have drugs that selectively modulate protein function. One major axis of our research is to bring together these two fields, developing high-precision photocontrolled inhibitors or "photopharmaceuticals" which leverage spatiotemporally precise applications of light to pattern their bioactivity. Using light, we can target photopharmaceuticals spatially to particular cells or subcellular areas, and temporally by switching their activity on and off at will.

We work on (1) photoresponsive tubulin binders to modulate the microtubule cytoskeleton with spatiotemporal precision (Li, Adrian, Elena; Emmy Noether grant), (2) photoswitchable TRP channel inhibitors to study channel function (Markus, Alex; SFB152), and (3) light-controlled reagents for biophysics studies of heterogeneous systems such as membranes and gels (Philipp, SFB1032). We also develop new chemistries and methods to harness light in chemical biology, particularly (4) hybrid chemical systems for protein photocontrol (Ben, SPP1926).

Biology, chemistry, light: Probes and prodrugs for biological redox processes
The other major axis of our research is developing fluorogenic chemical probes to image redox enzymatic activity. Redox-active chemical probes remain an almost untapped resource in biology. By combining design and synthesis at the cutting edge, with the chemical biology background from our research in photoresponsive probes, Lukas, Jan, and Lena are pushing the boundaries of what chemical probes can achieve in cells and in vivo.

Our research methods rely on:

  • Developing biological methods to test and exploit high-spatiotemporal precision targeting of small bioactive molecules.
  • Using known structures and binding site information to design novel pharmacophore scaffolds that enable new layers of functionality in biological applications.
  • Using photoisomerisations, fluorescence, FRET, and photoreactivity with our new scaffolds, to generate functionally photoresponsive reagents for chemical biology.

See the specific research pages for more information.